Neuroscience Information Framework Ontologies: Nerve cells in Neurolex and NIFSTD

Maryann MartoneUniversity of California, San Diego

The Neuroscience Information Framework: Discovery and utilization of web-based resources

for neuroscience

http://neuinfo.org

UCSD, Yale, Cal Tech, George Mason, Washington Univ

Supported by NIH Blueprint

A portal for finding and using neuroscience resources

A consistent framework for describing resources

Provides simultaneous search of multiple types of information, organized by category

Supported by an expansive ontology for neuroscience

Utilizes advanced technologies to search the “hidden web”

Modular ontologies for neuroscience

NIF covers multiple structural scales and domains of relevance to neuroscience Incorporated existing ontologies where possible; extending them for neuroscience where necessary Normalized under the Basic Formal Ontology: an upper ontology used by the OBO Foundry Single inheritance Cross-domain relationships are being built in separate files

NIFSTDNIFSTD

NS Function

NS Function

Molecule

Molecule

Investigation

Investigation

Subcellular AnatomySubcellular Anatomy

MacromoleculeMacromolecule GeneGene

Molecule Descriptors

Molecule Descriptors

TechniquesTechniques

ReagentReagent ProtocolsProtocols

CellCell

InstrumentsInstruments

Bill Bug

NS Dysfunction

NS Dysfunction

Quality

Quality

MacroscopicAnatomy

MacroscopicAnatomy

Organism

Organism

ResourceResource

Ontologies imported/used by NIF

Gene Ontology Biological Process ChEBI (Mireot) PATO PRO (Bridge) BIRNLex OBI (Bridge) Disease Ontology (Mireot) Foundational Model of Anatomy (Mireot) Gene Ontology Cellular Component (Bridge) Neuronames, BAMS (Mapped) Cell Ontology (don’t use)

Practical limitations imposed by tools and expertise; constantly addressing challenges involved in using community ontologies that are evolving in production information systems

NIF Cell Identity: Unique identifier

nlx_neuron_nt_090803

http://ontology.neuinfo.org/NIF/BiomaterialEntities/NIF-Neuron-NT-Bridge.owl#nlx_neuron_nt_090803

Asserted hierarchy: Unique types of neuron

Uniqueness assured by concatenating brain region with cell type Hippocampus CA1 pyramidal cell

Neocortex layer 2/3 pyramidal cell

Standard naming convention

Major brain region, subregion, distinguishing characteristics, cell

Bridge files: Cross module relations

A set of properties that define it, e.g., part of, has neurotransmitter, has role

Properties assigned at level of part of neuron where appropriate (brain region, molecule)

Others at level of cell class: spiny, physiological

Logical restrictions for defined classes: Necessary and sufficient conditions to identify members of that class

GABAergic neuron is any member of class neuron has neurotransmitter GABA

Gordon Shepherd, Giorgio Ascoli, Kei Cheung, Maryann Martone, Fahim Imam, Stephen Larson

Cerebellum Purkinje cell

soma

Cerebellum Purkinje cell

dendrite

Cerebellum Purkinje cell

axon

Cerebellum granule cell layer

Cerebellum granule cell layer

Cerebellum Purkinje cell

layer

Cerebellum Purkinje cell

layer

Cerebellum molecular layer

Cerebellum molecular layer

Has part

Has part

Has part

Is part of

Is part of

Is part of

Shared building blocks: Modular ontologies joined in bridge files

Calbindin

Cerebellum Purkinje neuron

Cerebellar cortexCerebellar cortex

Has part Has

part

Has part

IP3 receptor

NIF Molecule

NIF Anatomy

NIF Subcellular

Defined Classes Neuron by brain region

NIF Cell, NIF Subcellular, NIF Anatomy

Hippocampus neuron is a type of neuron has part soma is part of any part of hippocampus

Neuron by molecule NIF Cell, NIF molecule

Neurotransmitter GABAergic neuron

By molecular constituent Parvalbumin-containing neuron

Neuron by role Circuit role

Principal neuron vs intrinsic neuron

Functional role Sensory neuron, motor neuron

Neuron by morphological quality Spiny neuron Pyramidal neuron

Sometimes use OBO relations, sometimes short cuts that can be expressed in OBO relations

String vs concept based search

Currently ~250 proposed classes

Neuron qualities

What can account for signals here?

Neurons are highly ramifying and polarized cells

Properties assigned at level of part of neuron

Community contributions: Neurolex Semantic Wiki

Good teaching tool for the power of more formal semantics

Knowledge base easier to view, index and navigate

Lighter weight and more human friendly than more formal ontologies and tools

Build knowledge from basic lexical elements and a few relationships Categories are linked through

explicit properties

Currently over 10,000 category pages

Use relationship shortcuts that can be expressed in OBO relations

Working with international group of neuroscientists to contribute content covering different domains and develop new content

http://neurolex.org Stephen Larson and INCF

Detailed propertiesCustom form based interface

Olfactory bulb (main) mitral cell

New version just about to be released References for each attribute

Meant to be used by anyone Curators (me) go through and translate

Translated into NIFSTD once finalized Some short cut relations translated

e.g., soma located in = neuron has part soma is part of some brain region

Inferring the Mesoscale

The NIFSTD is expressed in OWL (Web Ontology Language) Supports reasoning and inference

Through integration with other ontologies covering gross anatomy and molecular entities, we are working to create inferences across scales

Analyze locally; infer globally If there’s an axon terminal, then

there must be an axon…

Stephen Larson

Desiderata1000’s of neuron types; one group can’t do

them allEarly efforts all concentrate on same cell types

(easy ones) INCF has opportunity to coordinate different

groups so we can aggregate effort

Standard set of properties and standard syntax for logical definitionsTrying to base them on REL, but we take shortcuts

for practical reasonsRelation to GO function